Description

The combination of Sitagliptin + Metformin HCl is a single-tablet medication used to treat type 2 diabetes. It combines two oral antidiabetic drugs with different but complementary mechanisms of action. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor, and Metformin HCl is a biguanide. This combination provides a more comprehensive approach to blood sugar control than either drug alone.

Indications

This combination therapy is primarily indicated for the treatment of type 2 diabetes mellitus. It is used in adults who have not achieved adequate glycemic control with Metformin monotherapy or who are already being treated with both sitagliptin and metformin as separate tablets.

This combination is also used as an initial therapy for patients who are likely to require a dual approach to manage their blood sugar effectively.

Mechanism of Action

The combination works by targeting two different aspects of glucose metabolism:

1. Sitagliptin (DPP-4 Inhibitor)

• Action: Sitagliptin works on the incretin system. It selectively inhibits the enzyme dipeptidyl peptidase-4 (DPP-4). This enzyme is responsible for breaking down a group of hormones called incretins (GLP-1 and GIP).
• Effect: By preventing their breakdown, sitagliptin increases the levels of active incretins in the body. These hormones then stimulate the pancreas to release insulin in a glucose-dependent manner (only when blood sugar is high) and suppress the release of glucagon, a hormone that increases blood sugar. This helps to control blood glucose levels after meals without a significant risk of hypoglycemia.

2. Metformin HCl (Biguanide)

• Action: Metformin works primarily in the liver, where it reduces the production of glucose. It does so by activating the enzyme AMP-activated protein kinase (AMPK).

• Effect: The activation of AMPK leads to several glucose-lowering effects:
  • Decreased Hepatic Glucose Production: It significantly reduces the liver’s production of glucose.
  • Increased Insulin Sensitivity: It increases the sensitivity of muscle and fat cells to insulin, which improves the uptake of glucose from the bloodstream.
  • Reduced Intestinal Glucose Absorption: It also reduces the absorption of glucose from the intestines.

Combined Effect

The combination of Sitagliptin and Metformin provides a synergistic effect that addresses multiple aspects of type 2 diabetes:

• Metformin tackles insulin resistance and reduces glucose production by the liver.

• Sitagliptin enhances the body’s natural ability to regulate blood sugar, particularly after meals, by boosting the incretin system.

This dual action leads to a powerful and comprehensive reduction in both fasting and post-meal blood glucose levels, improving overall glycemic control.